Difference in the effects of acetazolamide and ammonium chloride acidosis on ventilatory responses to CO2 and hypoxia in humans.

Abstract

The effects of acetazolamide, a potent carbonic anhydrase inhibitor, and ammonium chloride (NH4C1) on arterial blood gas tension, resting ventilation, and ventilatory responses to CO2 (HCVR) and hypoxia (HVR) were studied in healthy male subjects. Both drugs induced chronic metabolic acidosis with the reduction in plasma bicarbonate by a mean of 7.0 ± 2.0 (S.D.) mM after acetazolamide and by 5.6 ± 1.8 mM after NH4Cl. The ratio in the decrement of Paco2 to that of plasma bicarbonate (d Paco2/d [HC03 ]) was 1.51 in the former and 0.98 in the latter. Both drugs increased inspiratory minute ventilation (Vi) predominantly due to increased tidal volume (VT) with acetazolamide and to increased respiratory frequency (f) with NH4Cl. In HCVR, the increments in C02-ventilation slope and in ventilation at PETco2 60 mmHg after drug administration were 0.77 ± 0.51 l • min -1 • mmHg -1 and 20.0± 11.2 1/mmn with acetazolamide and 0.59 ± 0.40l • min -1 • mmHg -1 and 8.0 ± 2.8 1/mmn with NH4Cl, respectively. On the other hand, HVR both in terms of d Vi/ASao2 slope and of ventilation at Sao2 75% significantly increased after NH4Cl but not after acetazolamide administration. Thus, augmented VT and HCVR in the acetazolamide group and increased f and HVR in the NH4C1 group suggested that the central chemosensitive mechanism in the former and the peripheral chemosensitive mechanism in the latter may predominantly be responsible for the elevated ventilatory activities.

Changes in Chemoreflex Characteristics Following Acute Carbonic Anhydrase Inhibition in Humans a Rest

“…Our findings are in agreement with previous rebreathing experiments performed on rats (Adams & Johnson, 1990), but not with steady-state experiments performed on humans (Swenson & Hughes, 1993) or cats (Wagenaar et al 1998). They are also in agreement with findings reported from chronic ACZ studies using the rebreathing method (Tojima et al 1986;Bashir et al 1990). …”

“…One approach used to ascertain the central chemoChanges in chemoreflex characteristics following acute carbonic anhydrase inhibition in humans at rest Andrea Vovk*, James Duffin †, John M. Kowalchuk* ‡, Donald H. Paterson* and David A. Cunningham* ‡ § sensitivity following CA inhibition has been to measure the ventilatory response to COµ during chronic or acute ACZ administration. It is generally agreed that chronic administration of ACZ in humans (Tojima et al 1986;Bashir et al 1990;Swenson & Hughes, 1993) increases the hyperoxic and hypoxic hypercapnic ventilatory response, which is mostly due to renal metabolic acidosis (Maren, 1967). Although chronic studies have generally agreed, there have been conflicting reports from acute studies.…”

Combined treatment with acetazolamide and medroxyprogesterone in chronic obstructive pulmonary disease patients

“…In the current literature, the effects of MPA and ACET on the HVR are confounded by the fact that the same preand post-drug levels of PET,CO 2 were not always maintained [7,26]. HVR is not only determined by O 2 pressure but also by the prevailing PI,CO 2 .…”

Carbonic anhydrase inhibitors and ventilation: a complex interplay of stimulation and suppression

“…If acetazolamide (7 mg·kg -1 ) is given i.v., there is no change in the slope of the hypercapnic ventilatory response (HCVR) and no increase at all in ventilation with mild hypoxia in the first hour before a metabolic acidosis develops [36]. In contrast, with dosing over 24 h, by which time a metabolic acidosis is established, HCVR is increased [9,[36][37][38] and the hypoxic ventilatory response (HVR) is either unchanged [10,39] or increased [38,40]. In addition, the rate of response to a hypercapnic stimulus is reduced by half, both before and after a metabolic acidosis develops [36].…”